Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000914
UniProt IDQ9NZJ5
Primary gene name(s)EIF2AK3
Synonym gene name(s)PEK, PERK
Protein nameEukaryotic translation initiation factor 2-alpha kinase 3
Protein functionMetabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2, eIF-2-alpha/EIF2S1 on 'Ser-52' during the unfolded protein response, UPR and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response, UPR-induced G1 growth arrest due to the loss of cyclin-D1, CCND1. Involved in control of mitochondrial morphology and function. {ECO:0000250|UniProtKB:Q9Z2B5}.
Subcellular locationEndoplasmic reticulum membrane;
Single-pass type I membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NZJ5
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
angiogenesis [GO:0001525];
bone mineralization [GO:0030282];
calcium-mediated signaling [GO:0019722];
cellular response to amino acid starvation [GO:0034198];
cellular response to cold [GO:0070417];
cellular response to glucose starvation [GO:0042149];
chondrocyte development [GO:0002063];
eiF2alpha phosphorylation in response to endoplasmic reticulum stress [GO:0036492];
endocrine pancreas development [GO:0031018];
endoplasmic reticulum organization [GO:0007029];
endoplasmic reticulum unfolded protein response [GO:0030968];
ER overload response [GO:0006983];
insulin-like growth factor receptor signaling pathway [GO:0048009];
insulin secretion [GO:0030073];
negative regulation of myelination [GO:0031642];
negative regulation of translation [GO:0017148];
negative regulation of translational initiation in response to stress [GO:0032057];
ossification [GO:0001503];
peptidyl-serine phosphorylation [GO:0018105];
PERK-mediated unfolded protein response [GO:0036499];
positive regulation of gene expression [GO:0010628];
positive regulation of protein localization to nucleus [GO:1900182];
positive regulation of transcription from RNA polymerase I promoter [GO:0045943];
positive regulation of vascular endothelial growth factor production [GO:0010575];
protein autophosphorylation [GO:0046777];
protein homooligomerization [GO:0051260];
protein phosphorylation [GO:0006468];
regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation [GO:0060734];
regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway [GO:1902235];
regulation of translational initiation by eIF2 alpha phosphorylation [GO:0010998];
response to endoplasmic reticulum stress [GO:0034976];
response to manganese-induced endoplasmic reticulum stress [GO:1990737];
skeletal system development [GO:0001501]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
enzyme binding [GO:0019899];
eukaryotic translation initiation factor 2alpha kinase activity [GO:0004694];
identical protein binding [GO:0042802];
protein homodimerization activity [GO:0042803];
protein kinase activity [GO:0004672];
protein phosphatase binding [GO:0019903];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
integral component of endoplasmic reticulum membrane [GO:0030176];
membrane [GO:0016020];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction114840
Phylogenetic treeQ9NZJ5
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.04360233570457430.8941520745706380.931094380815852
AZA vs. DISU0.3518498930923580.2441345617085730.827729280970541
AZA vs. IL70.1558311027017710.4204818189105420.999311006273513
AZA vs. SAHA-0.06560147119780530.7887790721585860.944404744536818
DISU vs. CD30.2957419432719410.4216252681844950.554180608948777
DISU vs. IL7-0.2043325181850890.5155819363497390.835382382896852
DISU vs. SAHA-0.4166643672258680.1601373041125730.515977831637713
DMSO vs. AZA-0.07237701537533290.6685996153688331
DMSO vs. CD3-0.1268063704745440.6919611840026060.773380461235942
DMSO vs. DISU-0.4257866983795250.1510219177586780.649403660690562
DMSO vs. IL70.235407798698170.1935388303036430.70296721389243
DMSO vs. SAHA-0.0008515877523637890.997128547354260.999549535705062
HIV vs. Mock in Activation0.1741959371057770.7800420199028760.999983755607037
HIV vs. Mock in Latency0.01737917816744890.9166121618308550.999834320637052
IL7 vs. CD30.1208327898887280.7070065814273310.802412972970564
SAHA vs. CD3-0.1344764274558140.7036426465268260.783326784602147
SAHA vs. IL7-0.2254673061784540.3561581127635330.606498801603875
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.217964 0.124911
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
4G31 X-ray 2.2Å A=588-1093.
4G34 X-ray 2.7Å A=588-1093.
4M7I X-ray 2.3Å A=588-1093.
4X7H X-ray 2.0Å A=575-1094.
4X7J X-ray 2.3Å A=575-1094.
4X7K X-ray 1.8Å A=575-1094.
4X7L X-ray 1.9Å A=575-1094.
4X7N X-ray 2.3Å A=575-1094.
4X7O X-ray 2.6Å A=575-1094.
4YZS X-ray 3.1Å A/B=104-403.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp160; precursor inhibited by 21464971
Tat induces phosphorylation of 19009018

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)